NO-mediated vasodilation in the rat liver: Role of hepatocytes and liver endothelial cells

Background/Aims: Nitric oxide (NO) is a potent vasodilator. We investigated the mechanisms responsible for this effect in the liver.Methods: Isolated perfused rat liver and cultures of endothelial sinusoidal cells and hepatocytes were used.Results: L-arginine (10⁻³ M) and NO donor Sin-1 (10⁻⁵ M) respectively increased the liver flow by 52% (p<0.01) and 93% (p<0.01) vs controls. The NO synthase inhibitor N^w-nitro-L-arginine (10⁻³ M) and the guanylate cyclase inhibitor methylene blue (10⁻⁵ M) respectively decreased the basal liver flow by 26% and 16% (p<0.05) and inhibited the vasodilating effects of L-arginine. L-arginine (10⁻³ M) increased nitrite concentration in hepatocyte culture (77.25±7.40 μmol · 1⁻¹ vs 14.70±3.55 μmol · 1⁻¹ in controls; p<0.01) and in liver endothelial cell culture (0.36±0.09 μmol · 1⁻¹ vs 0.12±0.05 μmol · 1⁻¹ in controls; p<0.05). N^w-nitro-L-arginine inhibited the basal production and abolished the L-arginine-induced production of nitrites both in hepatocyte and in liver endothelial cell cultures. The concentration of nitrites in the hepatocyte supernatant rose from 14.70±3.55 μmol⁻¹ · 1⁻ to 150.50±45.55 μmol · 1⁻¹ in the presence of a combination of interleukin-1β, TNF a and interferon γ.Conclusions: Under basal conditions, NO regulates the vascular tone of liver circulation. Both liver endothelial cells and hepatocytes can be implicated. NO production by hepatocytes may increase during inflammation.